New Therapies of Neovascular AMD—Beyond Anti-VEGFs

Abstract

Neovascular age-related macular degeneration (nAMD) is one of the leading causes of blindness among the aging population. The current treatment options for nAMD include intravitreal injections of anti-vascular endothelial growth factor (anti-VEGF). However, standardized frequent administration of anti-VEGF injections only improves vision in approximately 30–40% of nAMD patients. Current therapies targeting nAMD pose a significant risk of retinal fibrosis and geographic atrophy (GA) development in nAMD patients. A need exists to develop new therapies to treat nAMD with effective and long-term anti-angiogenic effects. Recent research on nAMD has identified novel therapeutic targets and angiogenic signaling mechanisms involved in its pathogenesis. For example, tissue factor, human intravenous immune globulin, interferon-β signaling, cyclooxygenase-2 (COX-2) and cytochrome P450 monooxygenase lipid metabolites have been identified as key players in the development of angiogenesis in AMD disease models. Furthermore, novel therapies such as NACHT, LRR and PYD domains containing protein 3 (NLRP3) inflammasome inhibition, inhibitors of integrins and tissue factor are currently being tested at the level of clinical trials to treat nAMD. The aim of this review is to discuss the scope for alternative therapies proposed as anti-VEGFs for the treatment of nAMD.

Pathophysiology of Age-Related Macular Degeneration: Implications for Treatment

“…Some integrins are expressed during neovascularization processes linked to endothelial cell migration and proliferation. Hence, these two molecules are considered to be involved in the patho-genesis of nAMD and possible therapeutic targets [45]. In fact, intravitreal risuteganib is an integrin inhibitor, with antiapoptotic and antiantiogenic effects that may also improve mitochondrial activity, which has shown significant vision improvement in patients with nonexudative AMD without drug-related adverse events [61].…”

Novel therapies for proliferative retinopathies

“…These developments are based on compelling evidence connecting the onset and severity of neovascularization with preceding and/or concomitant processes involving oxidative stress and inflammation. 53 For instance, patients with diabetic macular journals.sagepub.com/home/taj TherapeuTic advances in chronic disease edema (DME) have shown elevated concentrations of different pro-angiogenic factors besides VEGF-A (e.g. Ang2, erythropoietin, and soluble matrix metalloproteinase-2 and soluble matrix metalloproteinase-9), but also inflammation molecules [e.g.…”

“…Further studies are expected to provide greater insights on the mechanism of action and efficacy. 53 Phase II clinical trials have been performed in patients with wet AMD refractory to anti-VEGF therapy, showing promising results. 66,67 AR-13503.…”

Nove mogućnosti liječenja „suhe” senilne makularne degeneracije

“…Posljednjih godina u kliničku praksu uvedena je primjena intravitrealnih injekcija antivaskularnog endotelijalnog faktora rasta (engl. antivascular endothelial growth factor, anti-VEGF), što je pratio i razvoj novijih lijekova koji su ciljali pojedine segmente puta nastajanja neovaskularizacije, što je dovelo do revolucije u liječenju neovaskularne forme AMD-a [6][7][8][9] . Do sada nijedna terapija nije potvrđena i odobrena za lije- Za osobe s blagim ili intermedijarnim AMD-om 15-godišnja kumulativna incidencija nAMD-a približno je 2.0 %, a za progresiju u čisti GA otprilike 1,3 % 18 .…”